Plants, like all higher eukaryotes, must control the onset and spread of cell death during development and in response to environmental signals. Plant biology is replete with examples of developmentally programmed cell death (PCD). A specialized form of PCD in plants, termed the Hypersensitive Response (HR) is tightly correlated with successful recognition of, and responseto, pathogen infection. The HR is an important part of the plant immune response. HR is associated with an oxidative burst and signaling of pro-and anti-death signals to cells surrounding the infection site. While much is known about the molecular mechanisms of PCD control in animals, very little is known in plants. This proposal uses Arabidopsis as a genetic model with which to understand the control of HR as a paradigm for PCD in plants. The Arabidopsis genome is fully sequenced and there is little molecular evidence for significant conservation of key regulators of animal PCD at the sequence level. We were among the first to recognize the use of Arabidopsis to genetically dissect cell death control and have made significant contributions to the field. We identified and analyzed a series of mutants that mis-regulate HR-like cell death in the absence of pathogen. We cloned three key HR regulators all belonging to one gene family: LSD1 and the related genes LOL1 (LSD One Like 1) and LOL2. LSD1 acts to suppress the spread of unwanted cell death following a normal HR. Superoxide derived from a plasma membrane NADPH oxidase acts in concert with LSD1 in this process. We recently demonstrated that LSD1 interacts with several proteins, including functionally relevant transcription factors (TFs) and putative """"""""metacaspases"""""""".We demonstrated that one TF of the bZIP class, functions in HR and in basal defense to infection. Its activity is antagonized by LSD1, and they interact with in vivo. We intend to charaterize the role of the other LSD-interacting TFs in cell death and HR in the coming proposal period. We also recently cloned a second suppressor of the idiosyncratic runaway cell death phenotype of the Isd1 mutant. Very surprisingly, this suppressor encodes a disease resistance protein of the NB-LRR class. This is the first time that an NB-LRR class protein has been implicated in any process other than pathogen recognition. We will investigate how this particular NB-LRR controls the spread of HR-like cell death. We also recently demonstrated that two of the three so-called """"""""metacaspases,"""""""" identified in Arabidopsis by informatics approaches, and carrying the zinc-finger domain that defines the LSD1 protein family, also function in HR and runaway cell death is Isd1. This is the first definition of a function for these proteins, and allows us to propose a detailed characterization of their action as postive cell death regulators.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM057171-11S1
Application #
7887640
Study Section
Cellular Signaling and Dynamics Study Section (CSD)
Program Officer
Singh, Shiva P
Project Start
2009-08-17
Project End
2010-07-31
Budget Start
2009-08-17
Budget End
2010-07-31
Support Year
11
Fiscal Year
2009
Total Cost
$185,039
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Coll, N S; Smidler, A; Puigvert, M et al. (2014) The plant metacaspase AtMC1 in pathogen-triggered programmed cell death and aging: functional linkage with autophagy. Cell Death Differ 21:1399-408
Bonardi, Vera; Cherkis, Karen; Nishimura, Marc T et al. (2012) A new eye on NLR proteins: focused on clarity or diffused by complexity? Curr Opin Immunol 24:41-50
Argueso, Cristiana T; Ferreira, Fernando J; Epple, Petra et al. (2012) Two-component elements mediate interactions between cytokinin and salicylic acid in plant immunity. PLoS Genet 8:e1002448
Coll, N S; Epple, P; Dangl, J L (2011) Programmed cell death in the plant immune system. Cell Death Differ 18:1247-56
Bonardi, Vera; Tang, Saijun; Stallmann, Anna et al. (2011) Expanded functions for a family of plant intracellular immune receptors beyond specific recognition of pathogen effectors. Proc Natl Acad Sci U S A 108:16463-8
Jaillais, Yvon; Belkhadir, Youssef; Balsemao-Pires, Emilia et al. (2011) Extracellular leucine-rich repeats as a platform for receptor/coreceptor complex formation. Proc Natl Acad Sci U S A 108:8503-7
Coll, Nuria S; Vercammen, Dominique; Smidler, Andrea et al. (2010) Arabidopsis type I metacaspases control cell death. Science 330:1393-7
Eitas, Timothy K; Dangl, Jeffery L (2010) NB-LRR proteins: pairs, pieces, perception, partners, and pathways. Curr Opin Plant Biol 13:472-7
Nishimura, Marc T; Dangl, Jeffery L (2010) Arabidopsis and the plant immune system. Plant J 61:1053-66
Todesco, Marco; Balasubramanian, Sureshkumar; Hu, Tina T et al. (2010) Natural allelic variation underlying a major fitness trade-off in Arabidopsis thaliana. Nature 465:632-6

Showing the most recent 10 out of 22 publications